Growth Factors in Breast Cancer

Dickson, Robert B.; Lippman, Marc E.

doi:10.1210/edrv-16-5-559

Cited by 337 publications

(147 citation statements)

References 171 publications

(213 reference statements)

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…More interestingly, high levels of gelatinases are significantly related to c-erbB-2 overexpression. c-erbB-2 overexpression has been described as an independent predictor of survival in breast cancer (Konecny et al, 2001), and its amplification has been reported for 20 -25% of breast cancer patients (Dickson and Lippman, 1995) associated with more aggressive clinicopathologic features (Sahin, 2000). In addition, recent clinical investigations (Berney et al, 1998;Allgayer et al, 2000) demonstrated an association between ERBB2 overexpression and tumour-associated proteolysis in gastric and colon cancer, suggesting a direct role for ERBB2 in invasion and metastasis through upregulation of proteolytic enzymes.…”

Section: Discussionmentioning

confidence: 99%

Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera

et al. 2004

View full text Add to dashboard Cite

Matrix metalloproteinases, in particular the gelatinases MMP-2 and MMP-9, have received great attention in recent years as putative tumour markers for clinical applications. The main reason for the observed interest is their easy detection in body fluids. Moreover, recent evidence has shown multiple functions of MMPs, rather than simply degrading ECM, which include the mobilisation of growth factors and processing of surface molecules. Several authors have reported increased levels of MMPs in a number of cancers, but clinical correlations in breast cancer are still fragmentary. Thus, the aim of the present research was to investigate the activity levels of circulating gelatinases in the sera of breast cancer patients by means of zymographic analysis, and correlate data with clinicopathological parameters. In all, 80 patients and 22 healthy volunteers were involved in this study. Sera were obtained prior to surgery. The clinical variables were: grading of tumours, tumour size, lymph node involvement, tumour staging, oestrogen and progesterone receptor levels (76 out of 80 cases), and c-erbB-2 levels (46 cases). The densitometric measures of MMP-2 and MMP-9 activity levels indicated that the average values of both gelatinase activities were significantly higher in breast cancers than in control sera (Po0.0001). In addition, our analysis showed for the first time that elevated activity levels of both gelatinases correlated only with c-erbB-2 overexpression (P ¼ 0.0273 for MMP-2 and P ¼ 0.0075 for MMP-9). An inverse correlation was observed with regard to oestrogen receptor expression (P ¼ 0.0075 for MMP-2 and P ¼ 0.0273 for MMP-9). Moreover, a borderline inverse correlation was observed between the activity levels of both enzymes and nuclear grade (P ¼ 0.0511 for MMP-2 and P ¼ 0.0794 for MMP-9). In conclusion, the present data suggest that serum measures of MMP's activity may have diagnostic value for discriminating subgroups of breast cancer patients and support the hypothesis that ERBB2 amplification and/or overexpression enhance signalling pathways that may lead to increased production of gelatinases in c-erbB-2 positive breast cancers with higher metastatic potentialities.

show abstract

Section: Discussionmentioning

confidence: 99%

Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera

et al. 2004

View full text Add to dashboard Cite

show abstract

“…The mechanism underlying this effect was specified when ER-positive breast cancer cell lines became available. Estrogens directly increased the growth of breast cancer cells in culture by increasing the number of G0/G1 cells entering into the cell cycle [64,65]. Antiestrogens are competitive inhibitors of endogenous estrogens and inhibit the mitogenic activity of estrogens in breast cancer.…”

Section: Direct Evidences Of the Mitogenic Effect Of Estrogensmentioning

confidence: 99%

“…The initial and current hypothesis is that estrogens control the growth of primary breast cancers by inducing estrogen-regulated proteins that function as autocrine, paracrine or intracrine growth factors [65]. Estrogens activate (and antiestrogens block) genes controlled by estrogen-responsive elements (EREs).…”

Section: Involved Mechanisms?mentioning

confidence: 99%

“…The genes responsible for the mitogenic effect of estrogens have not been definitively determined but they probably include secreted growth factors [65], growth factor receptors [69,70], proteases such as cathepsin D [71] and cyclin/cdk factors [67]. The implication of molecules interfering with the cytoskeleton, such as E-cadherin, a mediator of cell-cell interactions,as been also suggested [72].…”

Section: Involved Mechanisms?mentioning

confidence: 99%

See 1 more Smart Citation

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

Platet

Cathiard

Gleizes

et al. 2004

Critical Reviews in Oncology/Hematology

319

236

View full text Add to dashboard Cite

Estrogens play an important role in regulating the growth and differentiation of normal, premalignant and malignant cell types, especially breast epithelial cells, through interaction with two nuclear estrogen receptors (ER and ERIn this review, we present a brief overview of the actions of estrogens in the different steps of breast carcinogenesis, including cancer progression to metastasis, and of their clinical consequences in the prevention, prognosis and treatment of the disease. The requirement of estrogen receptors, mainly of the alpha subtype, in normal mammary gland differentiation and growth has been evidenced by estrogen receptor deficiency in animals. The promotion of breast cancer carcinogenesis by prolonged exposure to estrogens is well-documented and this has logically led to the use of antiestrogens as potentially chemopreventive agents. In breast cancer progression, however, the exact roles of estrogen receptors have been less well established but they may possibly be dual. Estrogens are mitogenic in ER-positive cells and antiestrogens are an efficient adjuvant therapy for these tumors. On the other hand, the fact that estrogens and their receptors protect against cancer cell invasiveness through distinct mechanisms in experimental models may explain why the presence of ER is associated with well-differentiated and less invasive tumors.2

show abstract

“…Signal transduction from the EGFR is initiated when ligand binding stimulates receptor dimerization and tyrosine autophosphorylation on multiple carboxy-terminal tyrosines, which then act as high-affinity binding sites for effector proteins [25]. EGFR signaling pathways regulate proliferation of normal mammary epithelial cells [26][27][28] and of ER(+) hormone-dependent HBC cells [29].…”

Section: Introductionmentioning

confidence: 99%

Retinoids arrest breast cancer cell proliferation: retinoic acid selectively reduces the duration of receptor tyrosine kinase signaling

Tighe

Talmage

2004

Experimental Cell Research

View full text Add to dashboard Cite

Retinoic acid (RA) induces cell cycle arrest of hormone-dependent human breast cancer (HBC) cells. Previously, we demonstrated that RA-induced growth arrest of T-47D HBC cells required the activity of the RA-induced protein kinase, protein kinase Cα (PKCα) [J. Cell Physiol. 172 (1997) 306]. Here, we demonstrate that RA treatment of T-47D cells interfered with growth factor signaling to downstream, cytoplasmic and nuclear targets. RA treatment did not inhibit epidermal growth factor (EGF) receptor activation but resulted in rapid inactivation. The lack of sustained EGFR activation was associated with transient rather than sustained association of the EGFR with the Shc adaptor proteins and activation of Erk 1/2 and with compromised induction of expression of immediate early response genes. Inhibiting the activity of PKCα, a retinoic acid-induced target gene, prevented the effects of RA on cell proliferation and EGF signaling. Constitutive expression of PKCα, in the absence of RA, decreased cell proliferation and decreased EGF signaling. RA treatment increased steady-state levels of the protein tyrosine phosphatase PTP-1C and all measured effects of RA on EGF receptor function were reversed by the tyrosine phosphate inhibitor orthovanadate. These results indicate that RA-induced target genes, particularly PKCα, prevent sustained growth factor signaling, uncoupling activated receptor tyrosine kinases and nuclear targets that are required for cell cycle progression.

show abstract

Growth Factors in Breast Cancer

Cited by 337 publications

References 171 publications

Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera

Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

Retinoids arrest breast cancer cell proliferation: retinoic acid selectively reduces the duration of receptor tyrosine kinase signaling

Contact Info

Product

Resources

About